This is a Program Project consisting of 7 components. The objectives of research are the study of metabolic abnormalities associated with mental retardation. A computer assisted gas-chromatograph/mass spectrometry system has been developed and is being applied to the detection of changes in body constituents that might be associated with mental retardation. Specific studies are being conducted on argininosuccinicuria, lactic acidosis, acyl-carnitine transferase deficiency, and abnormalities of the pyruvate deficiency, and abnormalities of the pyruvate dehydrogenase complex. The molecular abnormality of the enzyme deficiency diseases, metachromatic leukodystrophy, transferase deficiency galactosemia and phenylketonuria is being sought through the physio-chemical characterization of the respective normal enzymes from human sources and comparison with the defective enzymes isolated from tissues and cells of diseased individuals. This approach has become possible after the purification of normal arylsulfatase A (deficient in metachromatic leukodystrophy) from human liver and of galactose-1-P:uridyl transferase (deficient in galactosemia) from human red cells and after the successful isolation of the catalytically inactive "transferase" in pure form from the red cells of a galactosemic individual. BIBLIOGRAPHIC REFERENCES: Fogelman, A.M., Edmond, J. and Popjak, G. "Metabolism of Mevalonate in Rats and Man Not Leading to Sterols", J. Biol. Chem. 250: 1771-1775, 1975. Gibson, G., Jope, R. and Blass, J.P. "Reduced synthesis of acetylcholine accompanying impaired oxidation of pyruvic acid in rat brain minces", Biochem. J. 148: 17, l975.